SU-E-I-02: Size-Dependent Computed Tomography Histogram Analysis: Towards Breast Tissue Segmentation.

PURPOSE: To examine the effects of object size on scatter-corrected CT histograms to be used in threshold-based tissue segmentation. METHODS: A polyethylene cone filled with various concentrations of water and methanol mixtures, simulating glandular and adipose tissues, were imaged with our quasi-monochromatic dedicated breast CT, and scatter corrected using beam-stop array measurements. Images were reconstructed using iterative OSC, and individual coronal slices along the central axis of the cone were analyzed, with radii ranging from 3.25-6.25cm. Histograms from each slice were fit with two Gaussians (fluid filling and cone material) using nonlinear least squares methods, and the corresponding standard deviation and peak centroid of each filled material were evaluated as a function of object radius. Identical methods were applied to dedicated breast CT images of four patients for clinical comparison. RESULTS: Analysis of phantoms and breast data indicates low correlation between the standard deviation and object diameter. The centroids of the Gaussian peaks demonstrate an inverse linear relationship with increasing object size, independent of object material. The clinical datasets show a similar linear relationship between centroids and breast radius. CONCLUSIONS: Data indicate that using a linear combination of Gaussian distribution functions to segment breast tissue in scatter corrected, quasi-monochromatic cone beam dedicated breast CT is possible. An object size-independent variation of attenuation values may allow for consistent restraints on initial fit parameters, resulting in improved confidence using Gaussian curve fitting. Appropriate scaling of the size-dependent volume slices, or independent slice analysis, is necessary to minimize binning variability for accurate tissue segmentation using Gaussian curve fitting. This work is supported by National Institutes of Health (R01-CA096821) and NIH Training Grant (T32-EB007185). MPT is the inventor of this hybrid breast imaging technology, and is named as an inventor on the patent for this technology assigned to Duke (US Pat. #7,609,808). If this technology becomes commercially successful, MPT and Duke could benefit financially.

Bloody diarrhoea: a rare presentation of a systemic disease.

Bloody diarrhoea in adolescents is usually due to enteric infection or inflammatory bowel disease. We describe a patient with bloody diarrhoea and endoscopic features of colitis in association with a systemic vasculitis. Positive anti-proteinase-3 antineutrophil cytoplasmic antibodies and cutaneous vasculitis on biopsy confirmed the diagnosis of Wegener's granulomatosis. He was started on high dose steroids and cyclophosphamide but required plasmapheresis for a declining renal function. The case highlights the need for vigilance with common clinical problems, because a life-threatening condition may be averted by prompt recognition and urgent therapy with immunosuppressants.

Migration and maturation of human colonic dendritic cells.

Dendritic cells (DC) in the colon may regulate intestinal immunity but remain poorly characterized. In this study a CD11c(+)HLA-DR(+)lin(-) (CD3(-)CD14(-)CD16(-)CD19(-)CD34(-)) population has been identified by flow cytometry in cells obtained by rapid collagenase digestion of human colonic and rectal biopsies. These day 0 (d0) CD11c(+)HLA-DR(+)lin(-) cells comprised approximately 0.6% of the mononuclear cells obtained from the lamina propria, were endocytically active, and had the phenotype of immature DC; they were CD40(+) and expressed low levels of CD83 and CD86, but little or no CD80 or CD25. Similar d0 DC populations were isolated from the colonic mucosa of healthy controls and from both inflamed and noninflamed tissue from patients with Crohn's disease. The lamina propria also contained a population of cells capable of migrating out of biopsies during an overnight culture and differentiating into mature DC with lower levels of endocytic activity and high cell surface expression of CD40, CD80, CD86, CD83, and CD25. This mature DC population was a potent stimulator of an allogeneic mixed leukocyte (MLR). Overnight culture of cells isolated by enzymatic digestion on d0 yielded DC with a phenotype intermediate between that of the d0 cells and that of the cells migrating out overnight. Overnight culture of colonic cells in which DC and HLA-DR(+)lin(+) cells were differentially labeled with FITC-dextran suggested that some of the maturing DC might differentiate from HLA-DR(+)lin(+) progenitors. This study presents the first analysis of the phenotype, maturational status, and migratory activity of human gut DC.

Intractable vomiting due to a brainstem lesion in the absence of neurological signs or raised intracranial pressure.

The case of a 30 year old man who was believed to have a gastrointestinal motility disorder causing his chronic vomiting is reported. He had been well until 21 months previously when he had developed recurrent vomiting which would occur up to 10 times in a 24 hour period. Vomiting was not precipitated by eating and was not associated with any other symptoms. He had lost 25 kg in weight. A psychiatric assessment did not reveal a psychogenic cause for his vomiting. A brainstem magnetic resonance imaging scan revealed an area of low signal in the low midbrain just above the pons to the left of the midline. After gadolinium contrast injection the area enhanced. There was little or no mass effect, that is minimal displacement of normal structures, and minimal oedema. The appearance was that of a low grade or early brainstem tumour. There were no features of haemorrhage or infarct. The patient was managed with oral dexamethasone, resulting in prompt resolution of his symptoms. A search for a central neurological cause is recommended in a patient with unexplained persistent vomiting, even in the absence of other features to suggest a neurological problem. Autonomic function testing may provide additional information.

Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease.

BACKGROUND: Tumour necrosis factor-alpha (TNF alpha) is thought to have a central role in the pathogenesis of Crohn's disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNF alpha, is effective in modifying disease activity in patients with moderately active Crohn's disease. METHODS: In this double-blind, placebo-controlled study, 31 patients were randomly assigned to CDP571 (n = 21) or placebo (n = 10). The primary endpoint was change in Crohn's disease activity index 2 weeks after a single infusion of CDP571 (5 mg/kg), or human albumin as placebo. One patient who attended no follow-up assessments was excluded from the analyses (CDP571 group). FINDINGS: The median Crohn's disease activity index fell from 263 (IQR 186.5-323.5) at baseline to 167 (137.5-294.0) at 2 weeks in the CDP571-treated patients (p = 0.0003); the change in the placebo group (253 [240-334] to 247 [183-256]) was not significant. In the treated group, there were also significant differences between baseline and 2 weeks in Harvey-Bradshaw score (p = 0.0005), key symptom score (p = 0.049), alpha 1-glycoprotein concentration (p = 0.012), and erythrocyte sedimentation rate (p = 0.01); concentrations of C-reactive protein fell, but not significantly (p = 0.067). Six patients achieved remission (Crohn's disease activity index < or = 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group. INTERPRETATION: A single 5 mg/kg infusion of CDP571 reduced disease activity in Crohn's disease at 2 weeks. These data suggest that antibody neutralisation of TNF alpha is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study.

Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults.

BACKGROUND: Chronic idiopathic intestinal pseudo-obstruction, a syndrome of ineffectual motility due to a primary disorder of enteric nerve or muscle, is rare. AIMS: To determine the clinical spectrum, underlying pathologies, response to treatments, and prognosis in a consecutive unselected group of patients. METHODS: Cross sectional study of all patients with clinical and radiological features of intestinal obstruction in the absence of organic obstruction, associated with dilated small intestine (with or without dilated large intestine), being actively managed in one tertiary referral centre at one time. RESULTS: Twenty patients (11 men and nine women, median age 43 years, range 22-67) fulfilled the diagnostic criteria. Median age at onset of symptoms was 17 years (range two weeks to 59 years). Two patients had an autosomally dominant inherited visceral myopathy. Major presenting symptoms were pain (80%), vomiting (75%), constipation (40%), and diarrhoea (20%). Eighteen patients required abdominal surgery, and a further patient had a full thickness rectal biopsy. The mean time interval from symptom onset to first operation was 5.8 years. Histology showed visceral myopathy in 13, visceral neuropathy in three, and was indeterminate in three. In the one other patient small bowel motility studies were suggestive of neuropathy. Two patients died within two years of symptom onset, one from generalised thrombosis and the other from an inflammatory myopathy. Of the remaining 18 patients, eight were nutritionally independent of supplements, two had gastrostomy or jejunostomy feeds, and eight were receiving home parenteral nutrition. Five patients were opiate dependent, only one patient had benefited from prokinetic drug therapy, and five patients required formal psychological intervention and support. CONCLUSIONS: In a referral setting visceral myopathy is the most common diagnosis in this heterogeneous syndrome, the course of the illness is usually prolonged, and prokinetic drug therapies are not usually helpful. Ongoing management problems include pain relief and nutritional support.